Section B Changed Classes/Guidelines Final

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EPHMRA

ANATOMICAL CLASSIFICATION

GUIDELINES 2019

Section B

Changed Classes/Guidelines

Final Version

Date of issue: 24th December 2018

A3 FUNCTIONAL GASTRO-INTESTINAL DISORDER DRUGS R2003

A3A PLAIN ANTISPASMODICS AND ANTICHOLINERGICS R1993

Includes all plain synthetic and natural antispasmodics and anticholinergics.

A3B Out of use; can be reused.

A3C ANTISPASMODIC/ATARACTIC COMBINATIONS

This group includes combinations with tranquillisers, meprobamate and/or barbiturates except when they are indicated for disorders of the autonomic nervous system and neurasthenia, in which case they are classified in N5B4.

A3D ANTISPASMODIC/ANALGESIC COMBINATIONS R1997

This group includes combinations with analgesics. Products also containing either tranquillisers or barbiturates and analgesics to be also classified in this group. Antispasmodics indicated exclusively for dysmenorrhoea are classified in G2X1.

A3E ANTISPASMODICS COMBINED WITH OTHER PRODUCTS r2011

Includes all other combinations not specified in A3C, A3D and A3F. Combinations of antispasmodics and antacids are classified in A2A3; antispasmodics with antiulcerants are classified in A2B9. Combinations of antispasmodics with antiflatulents are classified here.

A3F GASTROPROKINETICS r2013

This group includes products used for dyspepsia and gastro-oesophageal reflux. Compounds included are: alizapride, bromopride, cisapride, clebopride, cinitapride, domperidone, levosulpiride, metoclopramide, trimebutine. Prucalopride is classified in A6A9.

Combinations of gastroprokinetics with other substances are classified here if used for dyspepsia or gastro-oesophageal reflux.

A3G GASTRO-INTESTINAL SENSORIMOTOR MODULATORS r2019

Products which are specifically developed to modulate the multiple symptoms of irritable bowel syndrome (IBS). Includes alosetron, tegaserod.

Linaclotide (290mcg) indicated for IBS-C (irritable bowel syndrome with constipation) is classified here; linaclotide (145mcg) indicated for chronic constipation is classified in A6A9. Products containing linaclotide for both chronic constipation and for IBS-C are classified here when there is no distinction by strength. Lubiprostone (8mcg) indicated for IBS-C is classified here; lubiprostone (24mcg) indicated for chronic constipation is classified in A6A9. Products containing plecanatide indicated for chronic constipation and IBS-C are classified here. Other drugs for constipation, including laxatives, are classified in A6A.

A6 DRUGS FOR CONSTIPATION AND BOWEL CLEANSERS r2014

Includes laxatives and other products for constipation. Products that are both laxatives and bowel cleansers are classified in the appropriate laxative class. For the classification of products indicated for irritable bowel syndrome with constipation (IBS-C) see A3G.

A6A DRUGS FOR CONSTIPATION r2014

A6A1 Faecal softening laxatives r2015

Includes products containing softening laxatives such as liquid paraffin or docusate sodium. Combinations of faecal softening laxatives with osmotic laxatives are classified here. Combinations with bulk-forming laxatives are classified in A6A3. Combinations with stimulant laxatives are classified in A6A2.

For castor oil products see A6A2. Glycerol suppositories are classified in A6A9.

A6A2 Stimulant laxatives r2013

Includes products containing laxatives that have a stimulant effect on the intestinal membrane and peristalsis. Many of these are herbal, eg senna, or of herbal origin (anthraquinones, emodines, glycosides, etc). This group also includes phenolphthalein-derivatives, bisacodyl, and sodium picosulphate when used as a laxative. Products containing a stimulant laxative in combination with other laxative substances (except bulk-forming) are classified here.

A6A3 Bulk-forming laxatives r2013

Includes products containing substances such as bran, ispaghula, methylcellulose, sterculia. Products containing a bulk-forming laxative in combination with other types of laxative are classified here.

A6A4 Enemas R2015

Includes all products for constipation in enema form. Other rectal forms for constipation are classified as appropriate in the other constipation classes. Glycerol suppositories and effervescent suppositories are classified in A6A9.

Combination packs containing an enema and another form are classified according to the other form.

A6A5 Out of use D2013

A6A6 Osmotic laxatives I2013

Includes products containing osmotic laxatives. Substances include lactitol, lactulose, macrogols, magnesium citrate, magnesium hydroxide, magnesium sulphate, mannitol, sorbitol, etc. Combinations with other laxative substances are classified in A6A1, A6A2 and A6A3. Combinations with electrolytes that are present to ensure a neutral impact on electrolyte levels are classified in A6A7.

A6A7 Osmotic laxatives with electrolytes I2013

Includes products containing osmotic laxatives in combination with electrolyte substances. These specific electrolytes are present to ensure a neutral impact on electrolyte levels.

A6A9 Other drugs for constipation r2019

Includes other drugs for constipation and combinations of laxatives not classified in A6A1-A6A7. Combinations of laxatives with centrally acting anti-obesity substances are classified in A8A.

Glycerol suppositories and effervescent suppositories are classified here.

Prucalopride for chronic constipation is classified here. Linaclotide (145mcg) indicated for chronic constipation is classified here; linaclotide (290mcg) indicated for IBS-C (irritable bowel syndrome with constipation) is classified in A3G. Products containing linaclotide for both chronic constipation and for IBS-C are classified in A3G when there is no distinction by strength. Lubiprostone (24mcg) indicated for chronic constipation is classified here; lubiprostone (8mcg) indicated for IBS-C is classified in A3G. Products containing plecanatide and indicated for both chronic constipation and IBS-C are classified in A3G.

A7 INTESTINAL DISORDER PRODUCTS r2019

Products for functional gastro-intestinal disorders are in A3 and products for constipation and bowel cleansing are in A6.

A7A INTESTINAL ANTI-INFECTIVES r2019

Includes all products containing one or more intestinal anti-infectives with or without other substances that are used for diarrhoea and/or hepatic encephalopathy. Sulphonamides and special antibacterials such as polymyxin, neomycin, vancomycin or colistin in oral form, when mainly indicated as antidiarrhoeals are included in this group. Combinations with motility inhibitors, intestinal adsorbants and micro-organisms are also included.

Products containing rifaximin for either diarrhoea or hepatic encephalopathy are classified here. Products containing fidaxomicin for Clostridium difficile intestinal infections are classified here.

A7B INTESTINAL ADSORBENT ANTIDIARRHOEALS r2011

Includes products such as kaolin and pectin. Combinations with micro-organisms are also included.

A7C Out of use; can be reused.

A7D Out of use; can be reused.

A7E INFLAMMATORY BOWEL DISORDER PRODUCTS R2017

Includes products for inflammatory bowel disorders. Immunosuppressant products used for inflammatory bowel disorders as well as other conditions are classified in L4, for example in L4B (anti-TNF products).

A7E1 Intestinal aminosalicylate products I2017

Includes products containing balsalazide, mesalazine, olsalazine, sulfasalazine and similar aminosalicylates for inflammatory bowel disorders. Products containing aminosalicylates and indicated for rheumatoid arthritis are classified in M1C.

A7E2 Intestinal corticosteroid products I2017

Includes products containing corticosteroids for inflammatory bowel disorders.

A7E9 Inflammatory bowel disorder products, other r2019

Includes other products for inflammatory bowel disorders. Products containing vedolizumab and indicated for inflammatory bowel disease only are classified here.

Products containing disodium cromoglicate and indicated for food allergy are classified here. 5

Darvadstrocel (allogenic stem cells) for perianal fistulae in Crohn’s disease are classified here.

A7F ANTIDIARRHOEAL MICRO-ORGANISMS I1993

Includes micro-organisms such as lactobacillus acidophilus which are indicated for the treatment of diarrhoeal disease. Excluded are combinations with other antidiarrhoeals such as anti-infectives, motility inhibitors and intestinal adsorbents.

A7G ORAL ELECTROLYTE REPLACERS I1993

Oral electrolyte replacers are included in this group where diarrhoeal disease has been indicated. Intravenous preparations are included in K.

A7H MOTILITY INHIBITORS I1993

Includes narcotic derivatives such as loperamide, diphenoxylate and paregoric. Combinations with intestinal adsorbents and micro-organisms are also included.

A7X INTESTINAL DISORDER PRODUCTS, OTHER r2019

Includes other products for intestinal disorders, including antidiarrhoeal products.

B BLOOD AND BLOOD FORMING ORGANS

B1 ANTITHROMBOTIC AGENTS R1994

B1A VITAMIN K ANTAGONISTS R2004

Includes coumarin and indanedione derivatives.

B1B HEPARINS R2004

B1B1 Unfractionated heparins

Includes injectable high molecular weight (unfractionated) heparin (pure and in combination with other substances) with an average molecular weight from 5000 up to 30000 Dalton. The molecules are unfractionated.

B1B2 Fractionated heparins R2003

Includes injectable low molecular weight (fractionated) heparin (pure and in combination with other substances) with an average molecular weight from 2000 up to 18000 Dalton. The molecules are fractionated (fragments). Included are, eg bemiparin, enoxaparin, tedelparin and tinzaparin.

B1B3 Heparins for flushing

Includes heparin products for use with catheters eg Hepflush, Heplock.

B1B9 Other heparins R2004

B1C PLATELET AGGREGATION INHIBITORS r2017

Includes all products claiming platelet aggregation inhibition as the main indication eg ticlopidine. Also included are those products which have specific packs or presentations which are mainly indicated for platelet aggregation inhibition. These products, such as sulphinpyrazone, ditazole, dipyridamole, aspirin and non-steroidal anti-inflammatories are also prescribed for other conditions.

B1C1 Cyclo-oxygenase inhibitor platelet aggregation inhibitors R2010

Includes specific presentations of eg acetylsalicylic acid (aspirin), indobufen, picotamide, sulfinpyrazone, which are mainly indicated for platelet aggregation inhibition.

All oral solid low-dose aspirin products (162mg and below) are classified in B1C1 worldwide.

B1C2 ADP (adenosine diphosphate) receptor antagonist platelet aggregation I2000 inhibitors

Includes clopidogrel and ticlopidine.

B1C3 GP IIb/IIIa (glycoprotein) antagonist platelet aggregation inhibitors I2000

Includes abciximab, eptifibatide and tirofiban.

B1C4 Platelet cAMP enhancing platelet aggregation inhibitors R2017

Includes prostacyclin derivatives eg beraprost, iloprost, limaprost and also phosphodiesterase (PDE) inhibitors eg anagrelide, dipyridamole when mainly indicated for platelet aggregation inhibition. Products containing epoprostenol are classified in C6B3. Products containing prostacyclin derivatives and only indicated for PAH are classified in C6B3. Products containing prostacyclin derivatives and indicated for both PAH and other conditions are classified here.

B1C5 Platelet aggregation inhibitors, combinations R2004

Includes combinations of two of more platelet aggregation inhibitors, eg a cyclo- oxygenase inhibitor with an ADP receptor antagonist, or a cyclo-oxygenase inhibitor with a PDE inhibitor.

Products containing a combination of a platelet aggregation inhibitor together with another substance and for use as antithrombotics are classified here.

B1C9 Other platelet aggregation inhibitors r2015

Includes eicosapentanoic acid, nizofenone, ozagrel, vorapaxar.

B1D FIBRINOLYTICS R2004

Includes endogenous proteins (eg urokinase), exogenous proteins (eg streptokinase) as well as ancrod, plasmin, plasminogen, tissue plasminogen activator (TPA), an anisoylated plasminogen-streptokinase activator complex (APSAC) and pro-urokinase (a precursor form of urokinase).

B1E DIRECT THROMBIN INHIBITORS I2004

Includes argatroban, bivalirudin, desirudin, lepirudin, melagatran, ximelagatran.

B1F DIRECT FACTOR XA INHIBITORS r2019

Includes products containing direct factor Xa inhibitors, eg apixaban, betrixaban, edoxaban, rivaroxaban.

B2D BLOOD COAGULATION

B2D1 Factor VIII, including substitutes r2019

Includes antihaemophilic globulin A, emcizumab, etc. Products containing von Willebrand factor only are classified in B2D9.

B2D2 Factors II, VII, IX and X

Includes antihaemophilic globulin B and prothrombin complex.

B2D3 Anti-inhibitor-coagulation complex R2003

Includes aPCC (activated prothrombin complex concentrate), activated FVII (FVIIa), and eptacog alfa.

B2D4 Factor XIII

B2D5 Fibrinogen

B2D6 Fresh frozen plasma and antihaemophilic plasma

B2D7 Cohn-Fraction I

B2D8 Platelet concentrates

B2D9 Other blood fractions R2005

Includes products containing von Willebrand factor (single ingredient).

B2E THROMBOPOIETIN AGONISTS I2012

Includes products containing thrombopoietin agonists, such as eltrombopag and romiplostim.

B2F TISSUE SEALING PREPARATIONS r2016

Includes products imitating the physiological process of fibrin formation which are used for tissue sealing, haemostasis and support of wound healing. Products containing thrombin/collagen for the prevention of bleeding prior to implantation of ICDs/pacemakers are classified here.

B2G SYSTEMIC HAEMOSTATICS r2019

Tissue extracts with haemostatic activity, and including snake venoms causing blood clotting, and hormone products exclusively promoted as haemostatics. Includes products containing parenteral conjugated oestrogens for control of uterine bleeding.

D5 NONSTEROIDAL PRODUCTS FOR INFLAMMATORY SKIN r2019 DISORDERS

Includes products for psoriasis, hyperkeratosis, ichthyosis, eczema, dermatitis, seborrhoea. Psoralens are classified here when used for inflammatory conditions. Excluded from this class are combinations with antibacterials (D6A), antifungals (D1A) and products specifically indicated in acne (D10A). Sulphur baths which contain other substances besides sulphur and are not used for dermatological purposes, are classified in M2A.

D5A TOPICAL ANTIPSORIASIS PRODUCTS r2019

Includes products containing substances such as tar, coal tar, ichthammol, dithranol, psoralens, salicylic acid for the treatment of psoriasis. These products may also be for other inflammatory skin conditions. Products containing corticosteroids in combination with coal tar or salicylic acid for psoriasis are classified here. These products may also be for other inflammatory skin conditions.

Includes products consisting of coal tar or calcipotriol, alone or in combination, when indicated for psoriasis.

D5B SYSTEMIC ANTIPSORIASIS PRODUCTS r2019

Includes products for the treatment of psoriasis. These products may also be for other inflammatory skin conditions. Products containing secukinumab or ustekinumab and indicated for psoriasis and also other non-skin conditions, eg arthritis, are classified in L4C. Psoriatic arthritis is defined as a skin condition. Apremilast is classified here if only for psoriatic skin conditions.

D5X OTHER NONSTEROIDAL PRODUCTS FOR INFLAMMATORY SKIN r2019 DISORDERS

Includes nonsteroidal products for inflammatory skin disorders which are not indicated for psoriasis. Specific topical immunomodulators for dermatitis are classified here.

Products containing ingenol mebutate or diclofenac gel that are indicated for actinic keratosis are classified here. Products containing aminolaevulinic acid for actinic keratosis, basal cell carcinoma or Bowen syndrome are classified in L1X8. Products containing topical fluorouracil for actinic keratosis are classified in L1B.

Products containing dupilumab for atopic dermatitis only are classified here. Products containing dupilumab for both atopic dermatitis and asthma are classified in L4C.

D7 TOPICAL CORTICOSTEROIDS

D7A PLAIN TOPICAL CORTICOSTEROIDS

Includes all dermatological products containing one or more corticosteroids and no other active ingredient. Topical anabolic steroids are classified in D3A.

D7B TOPICAL CORTICOSTEROID COMBINATIONS r2019

Includes all dermatological products containing corticosteroids in combination with one or more active ingredients, except those classified in D5A or D10A. It should be noted that, in the classification, the term antibacterial includes antibiotics, sulphonamides and antiseptics.

Also the basic criterion which determines the classification for products of this nature is the type of anti-infective product (antibacterial, antifungal or combination of the two) which is in combination with the corticosteroid. If the product in combination with the corticosteroid is not an anti-infective the product should be classified in D7B4.

D7B1 Combinations of corticosteroids with antibacterials r2019

If, in addition to corticosteroid and antibacterial or bacteriostatic (including antiseptic) agents (eg hexachlorophene) the product also contains non-anti- infective ingredients such as an antihistamine, local anaesthetic, oestrogen, urea, etc then it should still be classified in D7B1.

D7B2 Combinations of corticosteroids with antifungals

If, in addition to corticosteroids and antifungal agents, the product also contains non-anti-infective ingredients such as an antihistamine, local anaesthetic, urea, etc then it should still be classified in D7B2.

D7B3 Combinations of corticosteroids with antibacterials and antifungals

It should be noted that if a product contains not only corticosteroid + antibacterial + antifungal but also additional ingredients such as urea, an antihistamine, etc it should still be classified in D7B3.

D7B4 Other corticosteroid combinations r2019

Includes combinations of corticosteroids with all other types of products including, for example, antihistamines, local anaesthetics, etc. Combinations of corticosteroids with coal tar or salicylic acid and for psoriasis are classified in D5A; these products may also be for other inflammatory skin conditions as well as psoriasis.

D11 OTHER DERMATOLOGICAL PREPARATIONS

D11A OTHER DERMATOLOGICAL PREPARATIONS r2019

Includes medicated shampoos, medicated soaps, scalp lotions (other than in D5A, D1A3, D7B, D8A, D10A). Products for pigmentation disorders, systemic products for the treatment of dermatological conditions, anti-corn agents (plasters, tinctures, including products with salicylic acid especially formulated for warts, corns and calluses etc), and hair-restorers are classified in this group.

Products containing finasteride 1mg and for alopecia are classified here. Products containing finasteride 5mg and for BPH are classified in G4C3.

Products containing extracts of chamomile are classified in D3A.

Psoralens, when used for inflammatory conditions, are classified in D5.

Products containing sirolimus gel for tuberous sclerosis are classified here.

G2 OTHER GYNAECOLOGICALS

G2A UTEROTONIC PRODUCTS r2019

Includes products used to induce labour (including delivery of placenta) and/or to reduce postpartum haemorrhage. Includes oxytocics and prostaglandins E1 and E2, and products used for cervical dilatation.

G2B TOPICAL CONTRACEPTIVES

G2C Out of use; can be reused from 2000. D1997

G2D PROLACTIN INHIBITORS R1999

This group includes products used as prolactin inhibitors and containing bromocriptine, cabergoline, pergolide, quinagolide, terguride etc. Bromocriptine in lower doses (1 mg, 2.5 mg) for sexual disorders is classified here; higher doses for parkinsonism are in N4A. In Japan, bromocriptine is classified in N4A.

G2E LABOUR INHIBITORS I1997

This group includes products acting as labour inhibitors eg ritodrine.

G2F TOPICAL SEX HORMONES r2019

This group includes all topical hormones and/or steroids indicated for gynaecological conditions. Transdermal patches and vaginal formulations containing oestrogens and intended for a systemic effect are classified in G3C.

G2X OTHER GYNAECOLOGICAL PRODUCTS I1997

G2X1 Gynaecological antispasmodics I1997

This group includes oral analgesics and antispasmodics indicated exclusively for dysmenorrhoea.

G2X9 Other gynaecologicals r2016

Specific products included in this class are non-hormonal anti-inflammatories (eg benzydamine) which are indicated specifically to treat gynaecological conditions. Includes lubricants for intimate vaginal use only. Includes products (lactogogues) for the promotion of milk production.

Products containing paroxetine (7.5mg daily) and indicated for menopausal vasomotor symptoms are classified here.

Products containing flibanserin and indicated for hypoactive sexual desire disorder (HSDD) in women are classified here.

G3C OESTROGENS, EXCLUDING G3A, G3E, G3F r2019

Oestrogens in combination with non-hormonal substances are classified here.

Products containing a SERM in combination with an oestrogen and indicated for the short-term treatment of menopausal symptoms together with the prevention of osteoporosis are classified here.

Includes transdermal patches and vaginal formulations containing oestrogens and intended for a systemic effect.

Products containing parenteral conjugated oestrogens for uterine bleeding are classified in B2G.

G3D PROGESTOGENS, EXCLUDING G3A, G3F R1997

G3E ANDROGEN WITH FEMALE HORMONE COMBINATIONS

G3F OESTROGEN WITH PROGESTOGEN COMBINATIONS, EXCLUDING G3A

G3G GONADOTROPHINS, INCLUDING OTHER OVULATION STIMULANTS

G3H Out of use; can be reused from 2009. D2006

G3J SERMS (SELECTIVE OESTROGEN RECEPTOR MODULATORS) r2015

Included in this class are products that contain selective oestrogen receptor modulators, eg lasofoxifene, raloxifene. When primarily indicated for cancer, SERMs are classified in L2.

Products containing a SERM in combination with an oestrogen and indicated for the short-term treatment of menopausal symptoms together with the prevention of osteoporosis are classified in G3C.

G3X OTHER SEX HORMONES AND SIMILAR PRODUCTS r2015

Includes mammary extracts and other hormonal preparations for sexual disorders eg placenta extracts. Cyproterone acetate (tab 10mg) is classified here; higher doses (50 mg) and injectable forms are in L2B2 when used as cytostatics. Includes products containing tibolone.

Products containing mifepristone are classified here if indicated as abortifacients alone, or with other indications, or in G3A6 if indicated for emergency contraception.

Products containing ulipristal are classified here if indicated for uterine fibroids, or in G3A6 if indicated for emergency contraception.

H2 SYSTEMIC CORTICOSTEROIDS

H2A SYSTEMIC CORTICOSTEROIDS, PLAIN

Includes all systemic products containing one or more corticosteroid(s) and no other active ingredient, with or without lignocaine.

H2A1 Injectable corticosteroids, plain R1993

H2A2 Oral corticosteroids, plain R1993

H2A3 Other systemic corticosteroids, plain r2017

Includes suppositories. Corticosteroids to treat inflammatory intestinal disorders are classified in A7E2.

H2B SYSTEMIC CORTICOSTEROID COMBINATIONS r2019

Systemic products containing one or more corticosteroid(s) and one or more other active ingredient(s) (eg antihistamine). Also includes extracts containing natural corticosteroids, but excluding products classified in the following groups:

A7E2 – Intestinal anti-inflammatory agents

H4X – Liver extracts with small doses of corticosteroids (mainly in Italy).

G3X - Gland extracts (mammary, placenta, etc) and corticoid extracts mainly indicated for sexual disorders.

M1B - Corticosteroids with anti-inflammatory agents, analgesics, muscle relaxants, etc.

R1B – Systemic nasal preparations

R3D, R3F, R3L3 - Anti-asthmatic inhalants acting topically on the bronchioles.

J4 ANTIMYCOBACTERIALS R1993

J4A ANTITUBERCULAR PRODUCTS r2009

Includes all specific tubercular preparations as well as streptomycin and dihydrostreptomycin. Other antibacterials such as viomycin and cycloserine which are indicated specifically for tuberculosis are included as well as rifampicin and rifamycin where they are used mostly as tuberculostatics. Where rifampicin and rifamycin are indicated for several conditions, then they are classified in J1M.

The definition of ‘single ingredient’ means that only one specific antitubercular drug is present in the product. For example, if a product contains an antitubercular substance and also pyridoxine, this is a single ingredient product and will be classified in J4A1.

Kits include various different tablets or forms with different ingredients. Fixed dose products contain the ingredients in one dosage form.

J4A1 Antituberculars, single ingredient I2000

J4A2 Antituberculars, kits, four or more ingredients I2000

J4A3 Antituberculars, kits, three ingredients I2000

J4A4 Antituberculars, kits, two ingredients I2000

J4A5 Antituberculars, fixed dose, four or more ingredients I2000

J4A6 Antituberculars, fixed dose, three ingredients I2000

J4A7 Antituberculars, fixed dose, two ingredients I2000

J4A9 Antituberculars, others I2000

J4B DRUGS FOR THE TREATMENT OF LEPRA r2019

Includes preparations used for the treatment of lepra (eg aldesulphone, clofazimine, dapsone). Products containing thalidomide for cancer are classified in L1X2 and for erythema nodosum leprosum (ENL) in L4X. Products for both cancer and ENL are classified in L1X2.

L ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS R1994

L1 ANTINEOPLASTICS R2003

Includes all preparations mainly indicated for the treatment of cancers and all packs specifically produced for use in anticancer therapy eg special anticancer packs of antibiotics.

L1A ALKYLATING AGENTS R2003

Includes nitrogen mustard analogues (eg chlorambucil, chlormethine, cyclophosphamide, ifosfamide, melphalan, prednimustine, trofosfamide), ethylene imines (eg altretamine (hexamethylmelamine), carboquone, thiotepa, triaziquone), nitrosoureas (eg bendamustine, carmustine, fotemustine, lomustine, semustine, streptozocin), alkyl sulfonates (eg busulfan, mannosulfan, mitolactol, treosulfan), triazenes and analogues. Dacarbazine is classified in this group.

L1B ANTIMETABOLITES r2016

Includes folic acid analogues (eg methotrexate), pyrimidine analogues (eg capecitabine, carmofur, cytarabine, fluorouracil, tegafur) and purine analogues (eg fludarabine, mercaptopurine, tioguanine).

Methotrexate can also be classified in M1C for rheumatic conditions or in D for dermatological conditions.

Products containing topical fluorouracil for actinic keratosis are classified here.

L1C PLANT-BASED ANTINEOPLASTICS R2016

Includes products that contain plant-derived alkaloids, terpenes, lignans etc, or their derivatives/analogues.

Combination products containing substances from two fourth level classes of L1C are classified in the higher level class, eg a combination of a camptothecin with a podophyllotoxin is classified in L1C3.

L1C1 Vinca alkaloid antineoplastics I2016

Includes products containing alkaloids (or their derivatives/analogues) that are derived from Cantharanthus roseus (Madagascan periwinkle), eg vinblastine, vincristine, vindesine, vinflunine, vinorelbine, etc.

L1C2 Taxane antineoplastics I2016

Includes products containing diterpenes (or their derivatives/analogues) that are derived from species of Taxus (yew), eg cabazitaxel, docetaxel, paclitaxel, etc.

L1C3 Camptothecin antineoplastics I2016

Includes products containing alkaloids (or their derivatives/analogues) derived from Camptotheca acuminata (happy tree), eg hydroxycamptothecin, irinotecan, topotecan, etc.

L1C4 Podophyllotoxin antineoplastics I2106

Includes products containing lignans (or their derivatives/analogues) derived from Podophyllum (May apple) species, eg etoposide, mitopodozide, teniposide, etc.

L1C9 Plant-based antineoplastics, other I2016

Includes antineoplastic products containing other plant chemicals (or their derivatives/analogues), eg colchicine derivatives such as demecolcine.

Products for cancer containing omacetaxine mepisuccinate are classified here. Products for cancer containing Brucea javanica are classified here.

Antineoplastic products that contain dried plant material or unrefined plant extracts are classified in L1X9.

Antineoplastic products that are derived from natural sources other than plants, eg from bacteria or fungi, are classified elsewhere.

L1D ANTINEOPLASTIC ANTIBIOTICS r2019

Includes eg aclarubicin, bleomycin, dactinomycin, daunorubicin, doxorubicin, epirubicin, idarubicin, mitomycin, mithramycin, mitoxantrone, plicamycin, zorubicin.

Products containing mitoxantrone and indicated for both cancer and multiple sclerosis are classified here.

Products containing gemtuzumab ozogamicin and inotuzumab ozogamicin are classified in L1G9.

L1F PLATINUM ANTINEOPLASTICS I2014

Includes products containing eg carboplatin, cisplatin, oxaliplatin.

L1G MONOCLONAL ANTIBODY ANTINEOPLASTICS R2019

Antineoplastic monoclonal antibodies against protein kinases are classified here and not in L1H.

L1G1 Monoclonal antibody antineoplastics, CD20 I2019

Includes products containing obinutuzumab, ofatumumab, rituximab, rituximab with hyaluronidase, etc.

L1G2 Monoclonal antibody antineoplastics, VEGF/VEGFR I2019

Includes products containing bevacizumab, ramucirumab, etc.

L1G3 Monoclonal antibody antineoplastics, HER-2 I2019

Includes products containing margetuximab, pertuzumab, trastuzumab, trastuzumab emtansine, etc.

L1G4 Monoclonal antibody antineoplastics, EGFR I2019

Includes products containing cetuximab, necitumumab, nimotuzumab, panitumumab, etc.

L1G5 Monoclonal antibody antineoplastics, PD-1/PD-L1 I2019

Includes products containing atezolizumab, avelumab, cemiplimab, durvalumab, nivolumab, pembrolizumab, tislelizumab, etc.

L1G9 Monoclonal antibody antineoplastics, other I2019

Includes antibodies with other targets including other CD targets, CTLA-4 (ipilimumab), etc. Includes antibody drug conjugates (ADCs) if not classified with the target class (brentuximab vedotin, gemtuzumab ozogamicin, inotuzumab ozogamicin). Includes radio-labelled antibodies (ibritumomab tiuxetan, tositumomab iodine- 131).

Includes alemtuzumab, blinatumomab, brentuximab vedotin, catumaxomab, daratumumab, dinutuximab, elotuzumab, gemtuzumab ozogamicin, ibritumomab tiuxetan, inotuzumab ozogamicin, ipilimumab, mogamulizumab, olaratumab, racotumomab, rovalpituzumab tesirine, siltuximab, tositumomab, tositumomab iodine-131, etc.

Products containing alemtuzumab and indicated for cancer only are classified here.

Products containing alemtuzumab and indicated for multiple sclerosis are classified in N7A.

L1H PROTEIN KINASE INHIBITOR ANTINEOPLASTICS R2019

Antineoplastic monoclonal antibodies against protein kinases are classified in L1G.

L1H1 Protein kinase inhibitor antineoplastics, BCR-ABL I2019

Includes products containing bosutinib, dasatinib, imatinib, nilotinib, ponatinib, radotinib, etc.

L1H2 Protein kinase inhibitor antineoplastics, EGFR I2019

Includes products containing afatinib, dacomitinib, erlotinib, gefitinib, icotinib, olmutinib, osimertinib, varlitinib, etc.

L1H3 Protein kinase inhibitor antineoplastics, ALK I2019

Includes products containing alectinib, brigatinib, ceritinib, crizotinib, lorlatinib, etc.

L1H4 Protein kinase inhibitor antineoplastics, BRAF/MEK I2019

Includes products containing binimetinib, cobimetinib, dabrafenib, encorafenib, selumetinib, trametinib, vemurafenib, etc.

L1H5 Protein kinase inhibitor antineoplastics, CDK 4/6 I2019

Includes products containing abemaciclib, palbociclib, ribociclib, etc. Products containing both ribociclib and letrozole are classified here.

L1H9 Protein kinase inhibitor antineoplastics, other I2019

Includes all other protein kinase inhibitor antineoplastics, for example those inhibiting HER-2, JAK 1-2, BTK, Pi3K, etc.

Includes acalabrutinib, apatinib, axitinib, cabozantinib, everolimus, ibrutinib, idelalisib, lapatinib, lenvatinib, midostaurin, neratinib, nintedanib, pazopanib, regorafenib, ruxolitinib, sorafenib, sunitinib, temsirolimus, tivozanib, vandetanib, etc.

L1J PROTEASOME INHIBITOR ANTINEOPLASTICS I2018

Includes products containing proteasome inhibitors for neoplasms, eg bortezomib, carfilzomib, ixazomib, etc.

L1X ALL OTHER ANTINEOPLASTICS R2018

L1X1 Alternative preparations for cancer therapy r2018

Includes products derived from Viscum (mistletoe).

L1X2 Lidomide antineoplastics I2019

Includes products containing lenalidomide, pomalidomide or thalidomide for multiple myeloma and other cancers.

Products containing thalidomide for both cancer and erythema nodosum leprosum (ENL) are classified here. Products containing thalidomide for ENL only are classified in L4X.

L1X3 HDAC inhibitor antineoplastics I2018

Includes products containing HDAC inhibitors for neoplasms, eg belinostat, entinostat, panobinostat, romidepsin, tucidinostat, vorinostat, etc.

L1X4 PARP inhibitor antineoplastics I2019

Includes products containing niraparib, olaparib, rucaparib, talazoparib, veliparib, etc.

L1X5 CAR T-cell therapy antineoplastics I2019

Includes products containing axicabtagene ciloleucel, tisagenlecleucel, etc.

L1X8 Photosensitisers for cancer therapy r2019

Includes products containing photosensitisers for use in cancer therapy, eg aminolaevulinic acid, methyl aminolaevulinate, methoxsalen, porfimer, talaporfin, temoporfin, etc.

Products containing aminolaevulinic acid for actinic keratosis, basal cell carcinoma or Bowen syndrome are classified here. Products containing aminolaevulinic acid for use in diagnostic procedures are classified in T1X.

Products containing methoxsalen for other skin conditions such as psoriasis or vitiligo are classified in the appropriate D classes.

Products containing vertoporfin for macular degeneration are classified in S1P.

L1X9 All other antineoplastics r2019

Includes amsacrine, enzymes, estramustine, gallium nitrate, methylhydralazine, mitotane, procarbazine, substituted urea, tasonermin, vosaroxin. Also includes celecoxib for familial adenomatous polyposis (FAP).

Products containing aflibercept for cancer are classified here. Products containing aflibercept for macular degeneration are classified in S1P.

Includes products containing hedgehog pathway inhibitors, eg glasdegib, sonidegib, vismodegib, etc.

L2 CYTOSTATIC HORMONE THERAPY I1994

Includes all types of hormones used primarily in the treatment of cancers, eg adrenocorticoids, progestogens, oestrogens, anti-oestrogens and androgens.

L2A CYTOSTATIC HORMONES I1994

L2A1 Cytostatic oestrogens I1994

L2A2 Cytostatic progestogens I1994

L2A3 Cytostatic gonadotrophin-releasing hormone analogues R1995

Buserelin, deslorelin, goserelin, nafarelin, leuprorelin and triptorelin are classified here. When these substances are not used as cytostatics they are classified in H1C.

L2A9 Other cytostatic hormones I1994

Includes substances such as drostanolone, testolactone.

L2B CYTOSTATIC HORMONE ANTAGONISTS I1994

L2B1 Cytostatic anti-oestrogens R1997

Includes substances such as tamoxifen, mepitiostane, epitiostanol, toremifene.

L2B2 Cytostatic anti-androgens I1994

Includes substances such as flutamide, nilutamide. Cyproterone acetate (50 mg; injectable forms) is classified here.

L2B3 Cytostatic aromatase inhibitors r2019

Includes aminoglutethamide, anastrozole, exemestane, formestane, letrozole.

Products containing both ribociclib and letrozole are classified in L1H5.

L2B9 Other cytostatic hormone antagonists R2003

Includes fulvestrant.

L4 IMMUNOSUPPRESSANTS R2010

L4A Out of use; can be reused from 2013. D2010

L4B ANTI-TNF PRODUCTS r2019

Products containing anti-TNF substances are classified here, eg adalimumab, afelimomab, certolizumab pegol, etanercept, golimumab, infliximab. These products can be indicated for multiple conditions, eg rheumatoid arthritis, Crohn’s disease, psoriasis.

Products containing apremilast for psoriatic conditions only are classified in D5B.

L4C INTERLEUKIN INHIBITORS r2019

Includes products containing interleukin inhibitors, eg basiliximab, canakinumab, daclizumab, rilonacept.

Includes interleukin inhibitors indicated for the treatment of rejection in organ transplants and for auto-inflammatory diseases such as CAPS (cryopyrin- associated periodic syndromes).

Products containing tocilizumab or anakinra and indicated for arthritic conditions are classified in M1C. Products containing tocilizumab and indicated for both arthritic conditions and also giant cell arteritis are classified in M1C. Products containing secukinumab or ustekinumab and indicated for skin conditions such as psoriasis and also other non-skin conditions, eg rheumatoid arthritis, are classified here. Psoriatic arthritis is defined as a skin condition.

Products containing daclizumab and indicated for use in kidney transplantation are classified here. Products containing daclizumab and indicated for multiple sclerosis and other conditions are classified in N7A.

Products containing mepolizumab for asthma only or for asthma and EGPA (eosinophilic granulomatosis with polyangiitis) are classified in R3M.

Products containing dupilumab for atopic dermatitis are classified in D5X. Products containing dupilumab for both atopic dermatitis and asthma are classified here.

L4X OTHER IMMUNOSUPPRESSANTS r2019

Immunosuppressants used in the treatment of rejection in organ transplants are classified here, or in L4C if they contain interleukin inhibitors.

Includes eg antilymphocyte and antithymocyte immunoglobulins, azathioprine, cyclosporin, muromonab-cd3, mycophenolate mofetil, tacrolimus – unless classified elsewhere because of a specific indication or formulation. For example, ophthalmic cyclosporin for dry eye is classified in S1K9 and dermatological tacrolimus is classified in D5X.

Products for multiple sclerosis are classified in N7A. Products containing natalizumab and indicated for multiple sclerosis and other conditions are classified in N7A.

Products containing apremilast for psoriatic skin conditions only, are classified in D5B. Psoriatic arthritis is defined as a skin condition.

Products containing lenalidomide, pomalidomide or thalidomide for multiple myeloma and other cancers are classified in L1X2. Products containing thalidomide for both cancer and erythema nodosum leprosum (ENL) are classified in L1X2. Products containing thalidomide for erythema nodosum leprosum only are classified here.

Corticosteroids are not classified here.

M1C SPECIFIC ANTI-RHEUMATIC AGENTS r2019

This class includes abatacept, anakinra, tocilizumab, gold preparations, bucillamine, penicillamine and quinolines (eg oxycinchophen). Includes products containing mesalazine, olsalazine, and sulphasalazine if specifically indicated for rheumatic conditions. Products containing aminosalicylates and used for intestinal inflammatory conditions, are classified in A7E1.

Azathioprine is in L4X. Products containing methotrexate for rheumatic conditions are classified here; otherwise methotrexate is classified in LIB or in D.

Products containing anti-TNF substances are classified in L4B.

Products containing tofacitinib, and indicated for rheumatoid arthritis, are classified here.

Products containing interleukin inhibitors and only indicated for arthritic conditions are classified here, eg anakinra. Products containing tocilizumab and indicated for both arthritis and giant cell arteritis are classified here. Other interleukin inhibitors indicated for multiple conditions including arthritis are classified in L4C.

Psoriatic arthritis is defined as a skin condition.

M5 OTHER DRUGS FOR DISORDERS OF THE MUSCULO-SKELETAL SYSTEM

M5A Out of use; can be reused from 1996. D1993

M5B BONE CALCIUM REGULATORS R2002

Calcitonin products are classified in H4A. Products containing calcium only are classified in A12A and fluoride products are classified in A12C2.

M5B1 Out of use; can be reused from 2010. D2007

M5B2 Out of use; can be reused from 2010. D2007

M5B3 Bisphosphonates for osteoporosis and related disorders I2007

Includes products indicated and used mainly for osteoporosis and Paget’s disease, eg those containing alendronic acid, etidronic acid, ibandronic acid, risedronic acid, zoledronic acid, when indicated for these conditions. Combinations of bisphosphonates with calcium, calcitriol or colecalciferol are also classified here.

M5B4 Bisphosphonates for tumour-related calcium disorders I2007

Includes products indicated and used mainly for tumour-related calcium disorders (eg hypercalcaemia of malignancy) eg those containing clodronic acid, etidronic acid, ibandronic acid, pamidronic acid, zoledronic acid when indicated for these conditions.

M5B9 Other bone calcium regulators I2002

Includes other specific products which are used for osteoporosis (eg ipriflavone).

M5X ALL OTHER MUSCULOSKELETAL PRODUCTS r2019

Includes all other products for disorders of the musculoskeletal system not classified elsewhere. Includes musculoskeletal products containing substances such as cartilage extract, chondroitin, etc. Products containing chondroitin and glucosamine alone or in combination with other substances are classified here. Combinations of glucosamine with nonsteroidal anti-inflammatories are classified in M1A2. Topical glucosamine and chondroitin products are classified in M2A.

Includes hydroquinine indicated for restless leg syndrome.

Includes herbal products used for musculoskeletal pain.

Products containing burosumab for X-linked hypophosphataemia are classified here.

N7 OTHER CNS DRUGS R1996

N7A MULTIPLE SCLEROSIS PRODUCTS r2019

Products containing alemtuzumab, dimethyl fumarate, fingolimod, glatiramer acetate, laquinimod, teriflunomide, etc, and indicated for multiple sclerosis only, are classified here.

Products containing natalizumab and indicated for multiple sclerosis and other conditions are classified here.

Products containing alemtuzumab and indicated for cancer only, are classified in L1G9.

Products containing daclizumab and indicated for multiple sclerosis and also other conditions are classified here. Products containing daclizumab for use in kidney transplantation only are classified in L4C.

Products containing beta interferons and indicated for multiple sclerosis only are classified here. Products containing beta interferons and indicated for both multiple sclerosis and other conditions are classified in L3B2.

Products containing mitoxantrone and indicated for both cancer and multiple sclerosis are classified in L1D.

Products containing fampridine for improvement in walking in multiple sclerosis are classified in N7X.

Products containing other substances, eg corticosteroids, immunosuppressants such as azathioprine, that have multiple uses, are classified elsewhere.

N7B ANTISMOKING PRODUCTS

Includes products used to stop smoking.

N7C ANTIVERTIGO PRODUCTS I1996

Includes betahistine, cinnarizine and flunarizine when indicated for vertigo and Meniere's disease.

N7D ANTI-ALZHEIMER PRODUCTS I1998

N7D1 Anti-Alzheimer products, cholinesterase inhibitors R2003

Includes eg donepezil, galantamine, rivastigmine and tacrine.

N7D9 All other anti-Alzheimer products I1998

Includes all other products specifically used for Alzheimer's disease.

N7E DRUGS USED IN ALCOHOL DEPENDENCE R2002

Includes acamprosate, calcium carbimide, disulfiram. Naltrexone when used in alcohol dependence is classified here.

N7F DRUGS USED IN OPIOID DEPENDENCE R2002

Includes naltrexone, except when used in alcohol dependence (use N7E).

N7X ALL OTHER CNS DRUGS r2018

Includes parasympathetic agents. Benzodiazepine antagonists such as flumazenil are classified here. Atomoxetine is included in the class. Products containing gabapentin or pregabalin are classified in N3A if indicated for both neuropathic pain and epilepsy.

Products containing pilocarpine and indicated for both dry mouth and dry eye are classified here.

Products indicated for multiple sclerosis are classified in N7A. Products containing fampridine for improvement in walking in multiple sclerosis are classified here.

Products indicated for amytrophic lateral sclerosis (ALS) are classified here.

R3C NON-STEROIDAL RESPIRATORY ANTI-INFLAMMATORIES r2016

This group contains respiratory antihistamines and non-steroidal respiratory anti- inflammatory products. It includes azelastine, cromoglycic acid, ketotifen, levocabastine, and tranilast. In Japan only, terfenadine is included in this group. In other countries it is classified in R6A. Excluded are combinations of these compounds with B2-agonists (R3E).

R3C1 Non-steroidal respiratory anti-inflammatories, inhalant

R3C2 Non-steroidal respiratory anti-inflammatories, systemic

R3D CORTICOIDS r2019

Excluded are combinations of corticoids with B2-agonists (R3F) and LAMA/LABA combinations (R3L3).

R3D1 Corticoids, inhalant R2007

Includes plain inhalant corticosteroids only. Also includes products indicated for both rhinitis and asthma.

R3D2 Corticoids, systemic r2019

This subgroup includes combinations only, with the exception of those classified in R3F and R3L3.

Plain systemic corticosteroids are classified in H2A.

R3E B2-AGONIST AND R3C COMBINATIONS r2016

R3E1 B2-agonist and R3C combinations, inhalant r2016

R3E2 B2-agonist and R3C combinations, systemic r2016

R3F B2-AGONIST AND CORTICOID COMBINATIONS r2019

Combinations of LAMA/LABAs with corticosteroids are classified in R3L3.

R3F1 B2-agonist and corticoid combinations, inhalant r2016

R3F2 B2-agonist and corticoid combinations, systemic r2016

R3G Out of use D2016

R3G1 Out of use D2002

R3G2 Out of use D2016

R3G3 Out of use D2016

R3G4 Out of use D2016

R3H PDE4 INHIBITORS FOR ASTHMA/COPD I2005

Includes cilomilast, roflumilast.

R3H1 PDE4 inhibitors for asthma/COPD, inhalant I2005

R3H2 PDE4 inhibitors for asthma/COPD, systemic I2005

R3I DEVICES FOR ASTHMATIC CONDITIONS R2001

This excludes nebulising machines/nebulators which are classified in V7A.

R3J ANTILEUKOTRIENE ANTI-ASTHMATICS R2004

Includes montelukast, pranlukast, zafirlukast, and 5-lipoxygenase inhibitors such as zileuton when indicated for asthma.

R3J1 Antileukotriene anti-asthmatics, inhalant R1998

R3J2 Antileukotriene anti-asthmatics, systemic R1998

R3K ANTICHOLINERGICS, PLAIN I2016

R3K1 Short-acting anticholinergics, plain, inhalant I2016

Includes products containing eg, ipratropium bromide, oxitropium bromide, etc

R3K2 Long-acting anticholinergics, plain, inhalant I2016

Includes products containing eg aclidinium bromide, flutropium bromide, glycopyrronium bromide, tiotropium bromide, umeclidinium bromide, etc.

R3K3 Anticholinergics, plain, systemic I2016

Includes products containing anticholinergics (short- or long-acting) for systemic use.

R3L ANTICHOLINERGICS IN COMBINATION WITH B2-AGONISTS I2016

R3L1 Short-acting anticholinergic combinations with short-acting B2-agonists, I2016 inhalant

Includes products containing eg ipratropium bromide with fenoterol, ipratroprium bromide with salbutamol, etc

R3L2 Long-acting anticholinergic combinations with long-acting B2-agonists, r2019 inhalant

Includes products containing eg aclidinium bromide with formoterol, glycopyrronium bromide with indacaterol, tiotropium bromide with formoterol, tiotropium bromide with olodaterol, umeclidinium bromide with vilanterol, etc. These are known as LAMA/LABA combinations.

R3L3 Long-acting anticholinergic combinations with both long-acting B2-agonists I2019 and with corticosteroids, inhalant

Includes products containing a triple combination of a long-acting anticholinergic, a long-acting B2-agonist and a corticosteroid. Includes glycopyrronium bromide plus formoterol plus beclomethasone or budesonide, tiotropium bromide plus formoterol plus ciclesonide, umeclidinium bromide plus vilanterol plus fluticasone, etc.

R3L8 Anticholinergic combinations with B2-agonists, systemic I2016

Includes products containing anticholinergics (short- or long-acting) in combination with B2-agonists (short- or long-acting) for systemic use.

R3L9 Anticholinergic combinations with B2-agonists, inhalant, other I2016

Includes products containing anticholinergics in combination with B2-agonists that cannot be classified in the other R3L classes.

R3M INTERLEUKIN INHIBITOR ANTI-ASTHMATICS r2019

Includes products containing interleukin inhibitors for asthma, eg benralizumab, mepolizumab, reslizumab, etc.

Products containing mepolizumab for asthma only and for asthma and EGPA (eosinophilic granulomatosis with polyangiitis) are classified here.

R3X ALL OTHER ANTI-ASTHMA AND COPD PRODUCTS R2000

R3X1 All other anti-asthma and COPD products, inhalant R2003

This subgroup includes anti-asthmatic cigarettes.

R3X2 All other anti-asthma and COPD products, systemic r2018

Includes products containing alpha-1-proteinase inhibitor (alpha-1-antitrypsin).

V3X ALL OTHER THERAPEUTIC PRODUCTS r2019

Includes products with multiple anatomical effects, not readily classifiable in any single group. Large packs of chemicals (bulk packs) which are intended for preparation of formulations in the pharmacy/laboratory are classified here. Kelp products are classified here. Includes medical oxygen cylinders.

4th level used only in Germany and Hungary.